John Shacka received B.S. degrees in Biochemistry and Biology from Virginia Tech in 1991 and in 1997 received his Ph.D. in Pharmacology and Toxicology from the Medical College of Virginia Campus of Virginia Commonwealth University. After postdoctoral fellowships at NCI/NIH and at UAB, he joined faculty in the Dept. Pathology in 2009. He is currently an Assistant Professor in the Molecular and Cellular Pathology Division. The Shacka Lab studies the therapeutic potential for molecular targets in the autophagy-lysosome pathway to promote the clearance of toxic proteins that accumulate in experimental models of Parkinson's disease.

Targeting the Autophagy-Lysosome Pathway for Therapeutic Benefit in Parkinson's Disease

Description

The autophagy lysosome pathway (ALP) shuttles long-lived and/or damaged proteins and organelles to lysosomes for enzymatic degradation and recycling. The ALP thus provides energy to the cell and maintains intracellular quality control. Although the ALP is ordinarily a cell survival pathway, its function decreases with normal brain aging and in neurodegenerative diseases. Our lab studies ALP dysfunction in Parkinsonís disease (PD) and how it may contribute to the pathological accumulation of alpha-synuclein, a protein that has also been proposed to regulate PD pathogenesis. The Shacka Lab uses a combined in vitro (cell culture, genetic and biochemical assays) and in vivo (experimental animal models) approach to identify and validate candidate molecular targets for their ability to enhance the clearance of proteins that contribute to PD pathogenesis. In addition, we have recently initiated studies with postmortem and premortem tissues from PD patients with the ultimate goal of validating ALP-associated molecules as biomarkers for PD. We hope that these pre-clinical and translational investigations focused on ALP-specific molecules will elucidate rational therapeutic strategies that will ultimately delay the onset and progression of PD and other age-related neurodegenerative diseases.

Shacka, JJ and Roth, KA. Regulation of neuronal cell death and neurodegeneration by members of the Bcl-2 family: therapeutic implications. Current Drug Targets-CNS & Neurological Disorders. 4:25-39, 2005.